Effect of neutralizing sera on factor x-mediated adenovirus serotype 5 gene transfer.
The deployment of adenovirus serotype 5 (Ad5)-based vectors is hampered by preexisting immunity. When such vectors are delivered intravenously, hepatocyte transduction is mediated by the hexon-coagulation factor X (FX) interaction. Here, we demonstrate that human sera efficiently block FX-mediated cellular binding and transduction of Ad5-based vectors in vitro. Neutralizing activity correlated well with the ability to inhibit Ad5-mediated liver transduction, suggesting that prescreening patient sera in this manner accurately predicts the efficacy of Ad5-based gene therapies. Neutralization in vitro can be partially bypassed by pseudotyping with Ad45 fiber protein, indicating that a proportion of neutralizing antibodies are directed against the Ad5 fiber.
Parker
Alan L
AL
British Heart Foundation Glasgow Cardiovascular Research Centre, Division of Cardiovascular and Medical Sciences, 126 University Place, University of Glasgow, Glasgow G12 8TA, United Kingdom. ab11f@clinmed.gla.ac.uk
Waddington
Simon N
SN
Buckley
Suzanne M K
SM
Custers
Jerome
J
Havenga
Menzo J E
MJ
van Rooijen
Nico
N
Goudsmit
Jaap
J
McVey
John H
JH
Nicklin
Stuart A
SA
Baker
Andrew H
AH
D000256:Adenoviridae / Q000276:immunology*; D045744:Cell Line, Tumor; D005170:Factor X / Q000378:metabolism*; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors / Q000276:immunology*; D022781:Hepatocytes / Q000821:virology*; D006801:Humans; D007106:Immune Sera / Q000378:metabolism*; D009500:Neutralization Tests; D014161:Transduction, Genetic; D053585:Virus Attachment
D007106:Immune Sera; D005170:Factor X